Exploding bacteria for science!!!

As the Chief Medical Officer, Professor Dame Sally Davies, highlights today “danger posed by growing resistance to antibiotics should be ranked along with terrorism on a list of threats to the nation”. Professor Dame Sally Davies said diseases are evolving faster than the drugs that exist to treat them and antibiotic resistance is “a ticking time bomb“.

This is a subject of great interest to scientists in ICaMB, particularly the Centre for Bacterial Cell Biology, which brings together a world-class group of scientists researching bacterial physiology and the host response to bacterial infections. A major focus of this research involves:

  • Exploring alternative targets for antibiotic development
  • Understanding how antibiotics attack bacterial cells
  • Investigating how bacteria overcome such an attack

Tonight (March 11th 2013), work from the group of Kenn Gerdes and Etienne Maisonneuve, a post-doc in his group, will be featured on the BBC programme “Bang Goes the Theory” in an episode about Antibiotics.

Kenn and Etienne’s research focuses on persister cells, bacterial cells that can tolerate and survive attack by antibiotics.  Importantly, ALL bacteria analysed so far generate “persister cells” and understanding this is key to understanding how bacteria avoid antibiotic attack. “Bang Goes the Theory” will show a movie showing how these persister cells are identified in a bacterial population.

Penicillin inhibits synthesis of the bacterial cell wall, causing the cell to explode (or ‘lyse’) due to the high pressure inside the cell.  This is why penicillin and similar drugs are very effective in curing infections caused by penicillin-sensitive bacteria. In the movie, see how the cells suddenly explode when penicillin is added but notice how one cell, the persister cells (darker cells not exploding on the left panel) are surviving.

These persister cells evade killing by antibiotics because they grow extremely slowly. Persisters are proposed to be one explanation for infection relapses or chronic infections so Kenn and Ethienne’s work is extremely important for understanding how we should use antibiotics.

Microfluidic chamber used to make the movie

To do this work, Etienne used state-of-the-art technology – microfluidics – to follow the growth of individual bacterial cells under a microscope. These devices are smaller than a penny coin and the chambers where the bacteria are grown can be less than 1 mm across. This technique allows us to grow bacteria in one condition but, at a flip of a switch, change it and watch the response, as seen in the movie.

Year 9 student working on one of CBCB's microscopes


CBCB academics have used the ability to explode Escherichia coli to explore the what, when and how of antibiotics with Year 9 school students as part of the University engagement program Leading Edge.

With these students, we have developed a protocol to allow them to observe E. coli in the act of exploding after adding penicillin.

Exploding E. coli. Taken by Seaton Burn Community College Year 9 students

Persistence is not Resistance: It is important to understand the difference between these two terms. Antibiotic resistant and sensitive bacteria are able to generate persister cells, that are not effected by antibiotic attack. Antibiotic Resistance is a trait acquired by the whole population.

The Scientific Specifics: Over the last few years, several scientific breakthroughs made by the Gerdes group have, for the first time, given insight into how bacteria control the switch to slow growth and persistence. Persister cells can survive penicillin because the bacteria hibernate for a period, during which they don’t synthesize their cell wall.  They can then “wake up” when the antibiotic treatment is over, causing a new infection. In young and healthy people this is usually not a problem, because the rare non-growing bacteria are removed by the immune system. However, elderly individuals or those with a weakened immune system, it is often not efficient enough to permit clearance of the rare bacteria that survive the treatment, allowing the infection to “break out”.

The Gerdes group has shown that a certain class of gene that inhibits cell growth are turned on in one cell per 10,000. These discoveries open avenues to generate novel antibiotics and treatment regimes in the future. However, before that, their group is investigating if similar mechanisms allow pathogenic bacteria, such as Mycobacterium tuberculosis, to evade killing by antibiotics.


Institute of Cell and Molecular Biosciences
The Centre For Bacterial Cell Biology
Professor Kenn Gerdes
Bang Goes the Theory
Leading Edge

Bulging bacteria and the origins of life

Jeff (left), Romain (centre) and Yoshikazu (right), the team of researchers behind these exciting discoveries


In a paper published this week in CellJeff Errington’s team in ICaMB, have discovered new insights into the origin of life on Earth.


Jeff and his team share their results

Bacteria were the first organisms to appear on planet earth. Almost all modern bacteria have a tough protective shell called a cell wall. The structure of the wall and the mechanisms used by cells to manufacture it are conserved, suggesting that the wall was invented right at the beginning of bacterial evolution, and, therefore, when the first true cells emerged.

Production of cell wall is carefully regulated by complex machineries that allow the cell to enlarge and then divide in a controlled manner, all the time maintaining the integrity of the wall intact.

Despite its importance, it seems that many modern bacteria can survive cell wall loss under certain very special conditions, such as when they are treated with certain antibiotics that interfere with its production, like penicillin. Not only that, but a few years ago my lab showed that these “L-form” cells (named after the Lister Institute in London where they were first described) no longer need the complex mechanisms normally needed for bacterial growth and division. Instead, they grow by extrusion of irregular tubes or blebs of cytoplasm, that pinch off into daughter cells.

Our team – me, Yoshikazu KawaiRomain Mercier – has been working on this problem for some time. “Studying L-form biology is a real technical challenge, and this work could not have succeeded without the strong collaboration established between us“, says Romain. As Yoshikazu explains: “we developed a very simple genetic system to isolate mutations enabling L-form development from non-viable protoplasts.

We are excited because we think we have now solved the mystery of how L-forms grow and divide. Our latest results, published in Cell, show that the mechanism is remarkably simple: it requires only that cells make excess amounts of membrane – the thin porous layer that acts as the outer boundary of all cells, including our own.

Increasing the membrane surface area beyond the amount needed to contain the cytoplasm causes the cell to buckle and distort. Eventually, this leads to pinching off of membrane bags that are ill formed but nonetheless viable “baby” cells.

Time-lapse photography representing the division of B. subtilis without cell wall (L-form). The images were obtained using light microscopy. Scale bar: 3 μm

At first, we thought this mechanism was too simple to be true, we changed our minds when we were alerted to amazing experiments being done by several groups working on the origins of life, particularly Jack Szostak at Harvard, Saša Svetina in Ljubljana and Peter Walde in Zurich. These groups have been wondering how primitive cells could have arranged to grow and divide efficiently without spilling all of their contents. They recently found that simple membrane bags, called “vesicles”, can be induced to grow and reproduce into multiple smaller vesicles, in the test tube, just by increasing their surface area.

So, in explaining how the bizarre L-form bacteria manage to survive the loss of their beloved cell wall, we think we may now also have glimpsed how the first primitive cells could have duplicated themselves at the dawn of life on earth.

Jeff Errington 
Director of the Centre for Bacterial Cell Biology


Cell paper: http://www.cell.com/abstract/S0092-8674(13)00135-9
Cell website: http://www.cell.com/home see PaperFlick
Newcastle University Press Release:http://www.ncl.ac.uk/press.office/press.release/item/how-did-early-primordial-cells-evolve#.US-chen77jQ

Soapbox Science guest blogpost: http://www.blogs.nature.com/soapboxscience/2013/02/28/social-media-from-an-institutional-perspective-why-are-we-on-there

ICaMB website: http://www.ncl.ac.uk/camb/
Facebook: https://www.facebook.com/pages/ICaMB-Newcastle/416200498466481
Twitter: https://twitter.com/ICaMB_NCL
YouTube: http://www.youtube.com/channel/UCSuZgA6URiXTUoHq1tMe-PQ